Extracorporeal Blood Treatment Using Functional Magnetic Nanoclusters Mitigates Organ Dysfunction of Sepsis in Swine.

Mitigating sepsis-induced severe organ dysfunction with magnetic nanoparticles has shown remarkable advances in extracorporeal blood treatment. Nevertheless, treating large septic animals remains challenging due to insufficient magnetic separation at rapid blood flow rates (>6 L h-1) and limited incubation time in an extracorporeal circuit. Herein, superparamagnetic nanoclusters (SPNCs) coated with red blood cell (RBC) membranes are developed, which promptly capture and magnetically separate a wide range of pathogens at high blood flow rates in a swine sepsis model. The SPNCs exhibited an ultranarrow size distribution of clustered iron oxide nanocrystals and exceptionally high saturation magnetization (≈ 90 emu g-1) close to that of bulk magnetite. It is also revealed that CD47 on the RBCs allows the RBC-SPNCs to remain at a consistent concentration in the blood by evading innate immunity. The uniform size distribution of the RBC-SPNCs greatly enhances their effectiveness in eradicating various pathogenic materials in extracorporeal blood. The use of RBC-SPNCs for extracorporeal treatment of swine infected with multidrug-resistant E. coli is validated and found that severe bacteremic sepsis-induced organ dysfunction is significantly mitigated after 12 h. The findings highlight the potential application of RBC-SPNCs for extracorporeal therapy of severe sepsis in large animal models and potentially humans.

ASSOCIATIONS OF THE SERUM ALBUMIN CONCENTRATION AND SEQUENTIAL ORGAN FAILURE ASSESSMENT SCORE AT DISCHARGE WITH 1-YEAR MORTALITY IN SEPSIS SURVIVORS: A RETROSPECTIVE COHORT STUDY.

ABSTRACT: Introduction: This study was performed to investigate the predictors of 1-year mortality at discharge in sepsis survivors. Methods: This study was a retrospective analysis of patients with sepsis and septic shock at a single center. Patients who survived hospitalization for sepsis or septic shock between January 2016 and December 2017 were included in this study. Age, sex, body mass index, laboratory results such as blood cell count, C-reactive protein (CRP) and albumin levels, the Sequential Organ Failure Assessment (SOFA) score at the time of discharge and site of infection were compared between the survivors and nonsurvivors at 1 year postdischarge. Multivariate logistic regression was performed to identify the predictors of 1-year mortality. Results: During the study period, 725 sepsis patients were included in the analysis, 64 (8.8%) of whom died within the first year. The nonsurvivors were older and had a lower body mass index and a higher SOFA score at discharge than the survivors ( P < 0.05). Among the laboratory results at discharge, hemoglobin, platelet counts, and albumin concentrations were lower in the nonsurvivors than in the survivors, whereas CRP was higher in the nonsurvivors than in the survivors. In the multivariate logistic regression analysis, serum albumin <2.5 mg/dL and SOFA score ≥2 at discharge were identified as independent prognostic factors for 1-year mortality (odds ratio, 2.616; 95% confidence interval, 1.437-4.751 for albumin <2.5 mg/dL and 2.106, 1.199-3.801 for SOFA score ≥2, respectively). Conclusions: A low serum albumin concentration of <2.5 mg/dL and a high SOFA score of ≥2 at the time of discharge were prognostic factors for 1-year mortality in survivors of sepsis.

Feasibility study using longitudinal bioelectrical impedance analysis to evaluate body water status during fluid resuscitation in a swine sepsis model.

Fluid resuscitation is crucial in the initial management of sepsis; however, little is known about the serial changes and overall distribution of fluids administered into the body. To identify the feasibility of longitudinal bioelectrical impedance analysis during fluid treatment, a preclinical porcine model of Escherichia coli-induced sepsis was used. After sepsis induction, pigs were treated with fluid and vasopressors and monitored for up to 12 h after bacterial infusion or until death. Bipolar electrodes for bioelectrical impedance analysis were attached to the left extremities and measurements were performed every 10 min. Among the 12 subjects, 7 pigs expired during the experiment, and the median survival was 9.5 h. As sepsis progressed with an increase in cumulative fluid balance, R0 [∝ 1/extracellular water (ECW)] decreased, while Ri [∝ 1/intracellular water (ICW)] and ratio of extracellular water to total body water (ECW/TBW) increased. The phase angle constantly decreased throughout the monitoring period, and all non-survivors died when the phase angle decreased by more than 10%. Among the variables, ΔR0 and Δphase angle showed moderate negative correlations, and ΔECW/TBW showed a moderate positive correlation with the hourly fluid balance. Compared to survivors, a greater increase in ΔECW/TBW and a decrease in phase angle were observed in non-survivors over time, with an increase in cumulative fluid balance. Differences in ΔECW/TBW and phase angle emerged at 240 min when the difference in cumulative fluid balance between the two groups (survivors vs non-survivors) exceeded 1000 mL. In conclusion, continuous measurements of bioelectrical impedance analysis in a porcine sepsis model are feasible and may reflect changes in the body water profile during fluid resuscitation.

Changes in Biomarkers and Hemodynamics According to Antibiotic Susceptibility in a Model of Bacteremia.

Proper selection of susceptible antibiotics in drug-resistant bacteria is critical to treat bloodstream infection. Although biomarkers that guide antibiotic therapy have been extensively evaluated, little is known about host biomarkers targeting in vivo antibiotic susceptibility. Therefore, we aimed to evaluate the trends of hemodynamics and biomarkers in a porcine bacteremia model treated with insusceptible antibiotics compared to those in susceptible models. Extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli (E. coli, 5.0 * 10^9 CFU) was intravenously administered to 11 male pigs. One hour after bacterial infusion, pigs were assigned to two groups of antibiotics, ceftriaxone (n = 6) or ertapenem (n = 5). Pigs were monitored up to 7 h after bacterial injection with fluid and vasopressor support to maintain the mean arterial blood pressure over 65 mmHg. Blood sampling for blood culture and plasma acquisition was performed before and every predefined hour after E. coli injection. Cytokine (tumor necrosis factor-α, interleukin [IL]-1ß, IL-6, IL-8, IL-10, C-reactive protein, procalcitonin, presepsin, heparan sulfate, syndecan, and soluble triggering receptor expressed on myeloid cells-1 [sTREM-1]) levels in plasma were analyzed using enzyme-linked immunosorbent assays. Bacteremia developed after intravenous injection of E. coli, and negative conversion was confirmed only in the ertapenem group. While trends of other biomarkers failed to show differences, the trend of sTREM-1 was significantly different between the two groups (P = 0.0001, two-way repeated measures analysis of variance). Among hemodynamics and biomarkers, the sTREM-1 level at post 2 h after antibiotics administration represented a significant difference depending on susceptibility, which can be suggested as a biomarker candidate of in vivo antibiotics susceptibility. Further clinical studies are warranted for validation. IMPORTANCE Early and appropriate antibiotic treatment is a keystone in treating patients with sepsis. Despite its importance, blood culture which requires a few days remains as a pillar of diagnostic method for microorganisms and their antibiotic susceptibility. Whether changes in biomarkers and hemodynamics indicate treatment response of susceptible antibiotic compared to resistant one is not well understood to date. In this study using extended-spectrum ß-lactamase -producing E. coli bacteremia porcine model, we have demonstrated the comprehensive cardiovascular hemodynamics and trends of plasma biomarkers in sepsis and compared them between two groups with susceptible and resistant antibiotics. While other hemodynamics and biomarkers have failed to differ, we have identified that levels of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) significantly differed between the two groups over time. Based on the data in this study, trends of sTREM-1 obtained before the antibiotics and 2~4 h after the antibiotics could be a novel host biomarker that triggers the step-up choice of antibiotics.

Emergency physician-based intensive care unit for critically ill patients visiting emergency department.

BACKGROUND: To provide a prompt and optimal intensive care to critically ill patients visiting our emergency department (ED), we set up and ran a specific type of emergency intensive care unit (EICU) managed by emergency physician (EP) intensivists. We investigated whether this EICU reduced the time interval from ED arrival to ICU transfer (ED-ICU interval) without altering mortality. METHODS: This was a retrospective study conducted in a tertiary referral hospital. We collected data from ED patients who were admitted to the EICU (EICU group) and other ICUs including medical, surgical, and cardiopulmonary ICUs (other ICUs group), from August 2014 to July 2017. We compared these two groups with respect to demographic findings, including the Acute Physiology and Chronic Health Evaluation II (APACHE II) score, ED-ICU interval, ICU mortality, and hospital mortality. RESULTS: Among the 3440 critically ill patients who visited ED, 1815 (52.8%) were admitted to the EICU during the study period. The ED-ICU interval for the EICU group was significantly shorter than that for the other ICUs group by 27.5% (5.0 ±â€¯4.9 vs. 6.9 ±â€¯5.4 h, p < 0.001). In multivariable analysis, the ICU mortality (odds ratio = 1.062, 95% confidence interval 0.862-1.308, p = 0.571) and hospital mortality (odds ratio = 1.093, 95% confidence interval 0.892-1.338, p = 0.391) of the EICU group were not inferior to those of the other ICUs group. CONCLUSIONS: The EICU run by EP intensivists reduced the time interval from ED arrival to ICU transfer without altering hospital mortality.